IMMUNOREGULATION AND IMMUNE RECOGNITION IN FILARIASIS AND NON-FILARIAL DISEASES

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The purpose of this project is to delineate the mechanisms involved in regulating the humoral and cellular responses in patients with filariasis and other disease states and to determine those antigens responsible for inducing these responses. In vitro models of parasite-antigen driven antibody production as well as parasite-specific human T cell and B cell clones have been devloped to understand in more detail those mechanisms regulating antibody production (Particularly IgG and IgE) in filariasis, allergic diseases and in the normal situation. Further, HTLV-1 transformed T cell clones bearing T cell activation antigens and Fc epsilon receptors have been made in order to isolate fators involved in the T cell regulation of this isotype (IgE) which appears to be up-regulated in parasitic diseases. These T cells as well as a B cell line bearing the Fc epsilion receptor (FcER) have been used to isolate, purify, and raise antibody to the FcER which has recently enabled the gene for this receptor to be cloned molecularly. Qualitative analysis of the antigens recognized by the immune system at both a B and T cell level has been performed and T cell lines recognizing an Onchocerca volvulus species specific antigen has been constructed. Antigens recognized by human monoclonal antibodies derived from EBV-transformed patient B cells have also been identified. FPLC analysis of the antigenic components of filarial parasites has identified and helped to partially purify certain molecules which appear to regulate the immune response at both the cellular and humoral level human filariasis. Immunoblot analysis of filaria-specific IgE and IgG in loiasis, lyphatic filariasis and onchocerciasis have indicated patterns of antigen recognition which differ among groups of patients with different clinical manifestations of filariasis and among those with similar manifestations but who have been exposed to the parasite for different lengths of time.